Evidence MultiSTAT DOA Urine MultiPlex

K221550 · Randox Laboratories Limited · DJG · Oct 5, 2023 · Clinical Toxicology

Device Facts

• Record ID: K221550
• Device Name: Evidence MultiSTAT DOA Urine MultiPlex
• Applicant: Randox Laboratories Limited
• Product Code: DJG · Clinical Toxicology
• Decision Date: Oct 5, 2023
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3650
• Device Class: Class 2

Indications for Use

The Evidence MultiSTAT DOA Urine MultiPlex is intended for use with the Evidence MultiSTAT. The Evidence MultiSTAT is an analyzer intended for the qualitative determination of parent drug molecule and metabolites of drugs in human urine at the associated cutoffs. The Evidence MultiSTAT DOA Urine MultiPlex detects the following drugs at the following cut-offs: Phenobarbital (200 ng/ml), Tramadol (200 ng/ml), Phencyclidine (25 ng/ml), Buprenorphine (5 ng/ml), 6-Acetylmorphine (10 ng/ml). The Evidence MultiSTAT DOA Urine MultiPlex provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry (GC/MS) and/or Liquid Chromatography/Tandem Mass Spectrometry (LC/MS/MS) are the preferred confirmatory methods. Other chemical confirmation methods are available. Clinical consideration and professional judgement should be applied to any drug of abuse test result, particularly when preliminary positive results are obtained. For in vitro diagnostic use only.

Device Story

Evidence MultiSTAT DOA Urine MultiPlex is a benchtop, fully automated chemiluminescent immunoassay system for qualitative drug-of-abuse screening in human urine. The system utilizes a sealed biochip cartridge containing immobilized antibodies specific to drug classes. The principle of operation is a competitive immunoassay where drug in the sample competes with HRP-labeled drug derivatives for antibody binding sites; increased drug concentration reduces chemiluminescence. A CCD camera in the Evidence MultiSTAT analyzer quantifies light output. The device is intended for clinical laboratory use. Results are compared against a known cut-off material to classify samples as positive or negative. The output provides preliminary analytical results to assist healthcare providers in clinical decision-making, necessitating confirmation by GC/MS or LC/MS/MS.

Clinical Evidence

No clinical trials were performed. Performance was established via analytical bench testing and a method comparison study using 878 clinical urine samples. The device was compared against LC-MS/MS (or GC/MS for Phenobarbital) reference methods. Results demonstrated agreement across low negative, near cut-off negative, near cut-off positive, and high positive ranges. Interference studies evaluated exogenous compounds, pH, and specific gravity.

Technological Characteristics

Benchtop fully automated Biochip Array System. Core technology: solid-state biochip with immobilized antibodies. Detection: competitive chemiluminescent immunoassay using HRP-labeled drug derivatives and CCD camera. Reagents: phosphate/Tris buffers, luminol, peroxide. Connectivity: USB for batch-specific updates. Software: automated signal quantification.

Indications for Use

Indicated for the qualitative determination of parent drug molecules and metabolites of drugs of abuse (Phenobarbital, Tramadol, Phencyclidine, Buprenorphine, 6-Acetylmorphine) in human urine at specified cut-offs. For prescription use only.

Regulatory Classification

Identification

An opiate test system is a device intended to measure any of the addictive narcotic pain-relieving opiate drugs in blood, serum, urine, gastric contents, and saliva. An opiate is any natural or synthetic drug that has morphine-like pharmocological actions. The opiates include drugs such as morphine, morphine glucoronide, heroin, codeine, nalorphine, and meperedine. Measurements obtained by this device are used in the diagnosis and treatment of opiate use or overdose and in monitoring the levels of opiate administration to ensure appropriate therapy.

Special Controls

*Classification.* Class II (special controls). An opiate test system is not exempt if it is intended for any use other than employment or insurance testing or is intended for Federal drug testing programs. The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9, provided the test system is intended for employment and insurance testing and includes a statement in the labeling that the device is intended solely for use in employment and insurance testing, and does not include devices intended for Federal drug testing programs (*e.g.,* programs run by the Substance Abuse and Mental Health Services Administration (SAMHSA), the Department of Transportation (DOT), and the U.S. military).

Predicate Devices

• Profile-v MedtoxScan Drugs Of Abuse Test System (K091454)

Submission Summary (Full Text)

{0}

FDA

U.S. FOOD & DRUG

ADMINISTRATION

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

ASSAY ONLY

## I Background Information:

A 510(k) Number

K221550

B Applicant

Randox Laboratories Limited

C Proprietary and Established Names

Evidence MultiSTAT Urine DOA MultiPlex

D Regulatory Information

| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| DJG | Class II | 21 CFR 862.3650 - Opiate test system | TX - Clinical Toxicology |
| DIS | Class II | 21 CFR 862.3150 - Barbiturate Test System | TX - Clinical Toxicology |
| LCM | Unclassified | | |

## II Submission/Device Overview:

A Purpose for Submission:

New device

B Measurand:

Phenobarbital, Tramadol, Phencyclidine (PCP), Buprenorphine, 6-Acetylmorphine (6-MAM)

Food and Drug Administration

10903 New Hampshire Avenue

Silver Spring, MD 20993-0002

www.fda.gov

{1}

C Type of Test:

Chemiluminescent immunoassay

III Intended Use/Indications for Use:

A Intended Use(s):

See Indications for Use below.

B Indication(s) for Use:

The Evidence MultiSTAT DOA Urine MultiPlex is intended for use with the Evidence MultiSTAT. The Evidence MultiSTAT is an analyzer intended for the qualitative determination of parent drug molecule and metabolites of drugs in human urine at the associated cutoffs.

The Evidence MultiSTAT DOA Urine MultiPlex detects the following drugs at the following cut-offs:

| Analyte | Analyte in Cut Off Material | Cut-Off |
| --- | --- | --- |
| Phenobarbital | Phenobarbital | 200 ng/ml |
| Tramadol | Tramadol | 200 ng/ml |
| Phencyclidine | Phencyclidine | 25 ng/ml |
| Buprenorphine | Norbuprenorphine | 5 ng/ml |
| 6-Acetylmorphine | 6-Acetylmorphine | 10 ng/ml |

The Evidence MultiSTAT DOA Urine MultiPlex provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry (GC/MS) and/or Liquid Chromatography/Tandem Mass Spectrometry (LC/MS/MS) are the preferred confirmatory methods. Other chemical confirmation methods are available. Clinical consideration and professional judgement should be applied to any drug of abuse test result, particularly when preliminary positive results are obtained.

For In Vitro Diagnostic use only.

C Special Conditions for Use Statement(s):

Rx - For Prescription Use Only

D Special Instrument Requirements:

Evidence MultiSTAT

IV Device/System Characteristics:

A Device Description:

The Evidence MultiSTAT is a benchtop fully automated Biochip Array System analyzer. The Evidence MultiSTAT DOA Urine MultiPlex test kit components include a sealed urine test

K221550 - Page 2 of 18

{2}

cartridge which contains materials for the determination of the claimed analytes at the associated cut-off. This submission (K221550) represents the following claimed analytes and associated cut off concentrations; Phenobarbital at 200 ng/ml, Tramadol at 200 ng/ml, Phencyclidine at 25 ng/ml, Buprenorphine at 5 ng/ml, 6-Acetylmorphine at 10 ng/ml.

A sister submission (K220451) contains the review for the Evidence MultiSTAT and following Evidence MultiSTAT DOA Urine MultiPlex claimed analytes at the associated cut off concentrations; Methamphetamine at 500 ng/ml, Noroxycodone at 100 ng/ml, Benzodiazepines at 200 ng/ml, and Methadone at 300 ng/ml.

The Evidence MultiSTAT DOA Urine MultiPlex test kit will comprise of:

- 12 x Urine Test Cartridges
- 6 x 1mL Urine Cut Off Material (lyophilized)
- 4 x 1mL Urine Positive Control Material (lyophilized)
- 2 x 10mL Reconstitution Buffer
- 1 x USB which contains batch specific update and Instructions for Use (IFU)
- 1 x Batch Barcodes

Each kit is supplied with the Evidence MultiSTAT Accessory Kit which contains:

- 12 x MultiSTAT Tip Cartridges
- 1 x Tip/Waste Cartridge
- 6 x 1000 µl Pipette Tip
- 1 x Liquid Absorber

The Reagent Composition of the test kit will comprise:

MultiSTAT DOA Urine MultiPlex Assay Diluent - 20 mM phosphate buffer, pH 7.2 containing protein, detergents, and preservatives. This is contained within the cartridge.

- MultiSTAT DOA Urine MultiPlex Conjugate - 20 mM Tris based buffer, pH 7.0 containing protein, preservatives, and horseradish peroxidase - labelled drug derivatives. This is contained within the cartridge.
- MultiSTAT DOA Urine MultiPlex Biochip - Solid substrate containing immobilized antibody discrete test regions. This is contained within the cartridge.
- MultiSTAT DOA Urine MultiPlex Wash Buffer - 20 mM Tris buffered saline, pH 7.4, containing surfactant and preservatives. This is contained within the cartridge.
- LUM-EV934/PX - Luminol-EV934 and Peroxide are contained within the cartridge and are mixed in a ratio of 1:1 by the analyser to give the working signal reagent
- MultiSTAT DOA Urine MultiPlex Cut Off - Lyophilised, 20 mM phosphate buffer, pH 7.2 containing stabilizers, preservatives and drug concentrations at the assay cut off values.
- MultiSTAT DOA Urine MultiPlex Positive Control - Lyophilised, 20 mM phosphate buffer, pH 7.2 containing stabilizers, preservatives, and drug concentrations at 50% higher than the cut-off values.
- MultiSTAT Reconstitution Buffer – A solution at a neutral pH containing preservatives.

K221550 - Page 3 of 18

{3}

K221550 - Page 4 of 18

## B Principle of Operation:

The candidate device performs simultaneous detection of multiple analytes from a single sample. The core technology is the Randox Biochip, a solid-state device containing an array of discrete test regions containing immobilized antibodies specific to different Drugs of Abuse (DOA) compound classes. A competitive chemiluminescent immunoassay is used for the DOA assays with the drug in the specimen and drug labelled with horseradish peroxidase (HRP) being in direct competition for the antibody binding sites. Increased levels of drug in a specimen will lead to reduced binding of drug labelled with HRP and thus a reduction in chemiluminescence being emitted. The light signal generated from each of the test regions on the biochip is detected by a Charge Coupled Device (CCD) camera in the Evidence MultiSTAT analyzer which, together with the analyzer software, is used to quantify the light output and produce results. The tests employ a qualitative reporting method. Each test sample is assayed against the provided Cut Off material of known concentration, which is used to determine the classification of the samples based on the comparison of the signal output.

The immunoassay processes are performed automatically in a self-contained and sealed biochip cartridge, which holds the biochips, the reagents, wash buffer and other fluids required for the test to be conducted.

## V Substantial Equivalence Information:

### A Predicate Device Name(s):

Profile-v MedtoxScan Drugs Of Abuse Test System

### B Predicate 510(k) Number(s):

K091454

### C Comparison with Predicate(s):

| Device & Predicate Device(s): | K221550 | K091454 |
| --- | --- | --- |
| Device Trade Name | Evidence MultiSTAT DOA Urine MultiPlex | PROFILE®-V MEDTOXScan® Drugs of Abuse Test System |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | For the qualitative determination of drugs of abuse in human urine | Same |
| Assay Type | Competitive Immunoassay | Same |
| Sample Matrix | Urine | Same |
| Analyte (Cutoff ng/mL) | Phencyclidine (25 | Same |

{4}

| General Device Characteristic Differences | ng/mL) | |
| --- | --- | --- |
| Analyte | Buprenorphine (5 ng/mL)
Phenobarbital (200 ng/mL)
Tramadol (200 ng/mL)
6-Acetylmorphine (10 ng/mL) | Amphetamine (500 ng/mL)
Butalbital (200 ng/mL)
Benzodiazepines (150 ng/mL)
Cocaine (150 ng/mL)
Methamphetamine (500 ng/mL)
Methadone (200 ng/mL)
Morphine (100 ng/mL)
Oxycodone (100 ng/mL)
Propoxyphene (300 ng/mL)
THC Cannabinoids (50 ng/mL)
TCA Tricyclic Antidepressants (300 ng/mL) |
| Reagent Form | Ready to Use & Lyophilized | Ready to Use |

VI Standards/Guidance Documents Referenced:

CLSI EP12 – A2 – User Protocol for Evaluation of Qualitative Test Performance: Approved Guideline – Second Edition; 7-152

VII Performance Characteristics (if/when applicable):

A Analytical Performance:

1. Precision/Reproducibility:

A precision study was conducted using drug free negative urine that was spiked with the appropriate analyte at; -100%, -75%, -50%, -25%, +25%, +50%, +75%, +100%, of the cut off as well as at the cut off. The test was performed by at least two (2) operators on 4 instruments, with 40 replicates per lot. Representative data for each analyte is presented below:

K221550 - Page 5 of 18

{5}

| Phenobarbital | | | | | |
| --- | --- | --- | --- | --- | --- |
| Percent (%) of Cut Off | Concentration (ng/ml) | Number of determinations | Results | | % Agreement |
| | | | Negative | Positive | |
| -100% | 0 | 40 | 40 | 0 | 100 |
| -75% | 50 | 40 | 40 | 0 | 100 |
| -50% | 100 | 40 | 40 | 0 | 100 |
| -25% | 150 | 40 | 38 | 2 | 95 |
| Cut Off | 200 | 40 | 6 | 36 | N/A |
| +25% | 250 | 40 | 0 | 40 | 100 |
| +50% | 300 | 40 | 0 | 40 | 100 |
| +75% | 350 | 40 | 0 | 40 | 100 |
| +100% | 400 | 40 | 0 | 40 | 100 |
| Tramadol | | | | | |
| --- | --- | --- | --- | --- | --- |
| Percent (%) of Cut Off | Concentration (ng/ml) | Number of determinations | Results | | % Agreement |
| | | | Negative | Positive | |
| -100% | 0 | 40 | 40 | 0 | 100 |
| -75% | 50 | 40 | 40 | 0 | 100 |
| -50% | 100 | 40 | 40 | 0 | 100 |
| -25% | 150 | 40 | 37 | 3 | 92.5 |
| Cut Off | 200 | 40 | 1 | 39 | N/A |
| +25% | 250 | 40 | 0 | 40 | 100 |
| +50% | 300 | 40 | 0 | 40 | 100 |
| +75% | 350 | 40 | 0 | 40 | 100 |
| +100% | 400 | 40 | 0 | 40 | 100 |
| Phencyclidine (PCP) | | | | | |
| --- | --- | --- | --- | --- | --- |
| Percent (%) of Cut Off | Concentration (ng/ml) | Number of determinations | Results | | % Agreement |
| | | | Negative | Positive | |
| -100% | 0 | 40 | 40 | 0 | 100 |
| -75% | 6.25 | 40 | 40 | 0 | 100 |
| -50% | 12.5 | 40 | 40 | 0 | 100 |
| -25% | 18.75 | 40 | 39 | 1 | 97.5 |
| Cut Off | 25 | 40 | 2 | 38 | N/A |
| +25% | 31.25 | 40 | 0 | 40 | 100 |
| +50% | 37.5 | 40 | 0 | 40 | 100 |
| +75% | 43.75 | 40 | 0 | 40 | 100 |
| +100% | 50 | 40 | 0 | 40 | 100 |
| Buprenorphine | | | | | |
| --- | --- | --- | --- | --- | --- |
| Percent (%) of Cut Off | Concentration (ng/ml) | Number of determinations | Results | | % Agreement |
| | | | Negative | Positive | |
| -100% | 0 | 40 | 40 | 0 | 100 |
| -75% | 1.25 | 40 | 40 | 0 | 100 |

K221550 - Page 6 of 18

{6}

K221550 - Page 7 of 18

| 6-Acetylmorphine | | | | | |
| --- | --- | --- | --- | --- | --- |
| Percent (%) of Cut Off | Concentration (ng/ml) | Number of determinations | Results | | % Agreement |
| | | | Negative | Positive | |
| -100% | 0 | 40 | 40 | 0 | 100 |
| -75% | 2.5 | 40 | 40 | 0 | 100 |
| -50% | 5 | 40 | 40 | 0 | 100 |
| -25% | 7.5 | 40 | 36 | 4 | 90 |
| Cut Off | 10 | 40 | 0 | 40 | N/A |
| +25% | 12.5 | 40 | 0 | 40 | 100 |
| +50% | 15 | 40 | 0 | 40 | 100 |
| +75% | 17.5 | 40 | 0 | 40 | 100 |
| +100% | 20 | 40 | 0 | 40 | 100 |

2. Linearity:

Not applicable. These devices are intended for qualitative use only.

3. Analytical Specificity/Interference:

Potential interference from various compounds were tested by spiking the potentially interfering compound into drug-free urine containing the target drug concentrations at 50% below and 50% above the threshold cut off level. If interference was observed, the interferent was titrated down and the concentration at which no interference is observed quoted. The following exogenous compounds were found not to interfere with test results when tested up to the concentrations identified in the table below.

| Interference: Phenobarbital Assay | |
| --- | --- |
| Compound | Concentration Tested |
| Acetone | 1000 mg/dl |
| Ethanol | 1000 mg/dl |
| Glucose | 3000 mg/dl |
| Oxalic Acid | 100 mg/dl |
| Sodium Chloride | 6000 mg/dl |
| Caffeine | 1 mg/ml |
| Ascorbic Acid | 1500 mg/dl |
| Galactose | 10 mg/dl |
| Hemoglobin | 300 mg/dl |
| Riboflavin | 7.5 mg/dl |

{7}

K221550 - Page 8 of 18
| Acetaminophen | 1 mg/ml |
| --- | --- |
| Ibuprofen | 1 mg/ml |
| Creatinine | 5 mg/ml |
| Gamma Globulin | 500 mg/dl |
| Human Serum Albumin | 500 mg/dl |
| Urea | 3500 mg/dl |
| Acetylsalicylic Acid | 1 mg/ml |
| Ranitidine | 0.9 mg/ml |
| Oxazepam | 500,000 ng/ml |
| Clonazepam | 500,000 ng/ml |
| Alprazolam | 500,000 ng/ml |
| (±)-Methadone Hydrochloride | 500,000 ng/ml |
| (+) - Methamphetamine Hydrochloride | 500,000 ng/ml |
| Codeine Monohydrate | 500,000 ng/ml |
| MDEA HCl | 500,000 ng/ml |
| Nordiazepam | 500,000 ng/ml |
| Benzoylecgonine Tetrahydrate | 500,000 ng/ml |
| Morphine Sulfate Salt Pentahydrate | 500,000 ng/ml |
| Morphine-3-β-D-Glucuronide | 500,000 ng/ml |
| (-)-11-Nor-Δ9-THC Carboxylic Acid | 500,000 ng/ml |
| D-(+)-Amphetamine Sulfate | 500,000 ng/ml |
| (+)-Lorazepam | 500,000 ng/ml |
| (±)-MDMA | 100,000 ng/ml |
| Phencyclidine | 100,000 ng/ml |
| 6-Acetylmorphine | 100,000 ng/ml |
| (±)-MDA | 100,000 ng/ml |
| Flunitrazepam | 500,000 ng/ml |
| Nitrazepam | 500,000 ng/ml |
| Temazepam | 100,000 ng/ml |
| α Hydroxy Alprazolam | 100,000 ng/ml |
| Interference: Tramadol Assay | |
| --- | --- |
| Compound | Concentration Tested |
| Acetone | 1000 mg/dl |
| Ethanol | 1000 mg/dl |
| Glucose | 3000 mg/dl |
| Oxalic Acid | 100 mg/dl |
| Sodium Chloride | 6000 mg/dl |
| Caffeine | 1 mg/ml |
| Ascorbic Acid | 1500 mg/dl |
| Galactose | 10 mg/dl |
| Hemoglobin | 300 mg/dl |
| Riboflavin | 7.5 mg/dl |

{8}

K221550 - Page 9 of 18
| Acetaminophen | 1 mg/ml |
| --- | --- |
| Ibuprofen | 1 mg/ml |
| Creatinine | 5 mg/ml |
| Gamma Globulin | 500 mg/dl |
| Human Serum Albumin | 500 mg/dl |
| Urea | 3500 mg/dl |
| Acetylsalicylic Acid | 1 mg/ml |
| Ranitidine | 0.9 mg/ml |
| Salbutamol | 100,000 ng/ml |
| Sodium Fluoride | 10 g/L |
| (±) Metoprolol (+)Tartrate Salt | 100,000 ng/ml |
| Lisinopril | 100,000 ng/ml |
| Imipramine HCL | 100,000 ng/ml |
| (-) Nicotine | 500,000 ng/ml |
| Quetiapine Fumarate | 100,000 ng/ml |
| (S)- Duloxetine HCL | 100,000 ng/ml |
| Omeprazole | 100,000 ng/ml |
| Loratadine | 100,000 ng/ml |
| Carbamazapine | 100,000 ng/ml |
| Fluoxetine HCl | 500,000 ng/ml |
| Metformin hydrochloride | 100,000 ng/ml |
| Nortriptyline HCL | 100,000 ng/ml |
| Efavirenz | 100,000 ng/ml |
| Sodium Azide | 10 mg/ml |
| Ibuprofen | 500,000 ng/ml |
| Boric Acid | 10 mg/ml |
| Bupropion HCl | 500,000 ng/ml |
| Diphenhydramine hydrochloride | 100,000 ng/ml |
| Oxazepam | 500,000 ng/ml |
| (1S, 2S)-(+)-Pseudoephedrine | 100,000 ng/ml |
| Gabapentin | 100,000 ng/ml |
| Ciprofloxacin | 100,000 ng/ml |
| Cetirizine Dihychloride | 100,000 ng/ml |
| Alimemazine Hemitartrate | 100,000 ng/ml |
| (±)-Methadone Hydrochloride | 100,000 ng/ml |
| (+) - Methamphetamine Hydrochloride | 500,000 ng/ml |
| Zolpidem | 100,000 ng/ml |
| Citric Acid | 8 mg/ml |
| Potassium Chloride | 60 mg/ml |
| Bilirubin | 0.15 mg/ml |
| Codeine Monohydrate | 500,000 ng/ml |
| MDEA HCL | 500,000 ng/ml |

{9}

K221550 - Page 10 of 18
| Hydromorphone HCL | 100,000 ng/ml |
| --- | --- |
| Sertraline HCL | 75,000 ng/ml |
| L-Thyroxine | 100,000 ng/ml |
| Chlorpromazine HCl | 10,000 ng/ml |
| Clomipromine Hydrochloride | 50,000 ng/ml |
| Desipramine Hydrochloride | 100,000 ng/ml |
| Benzoylecgonine Tetrahydrate | 500,000 ng/ml |
| Morphine Sulfate Salt | 500,000 ng/ml |
| Pentahydrate | |
| Hydrocodone | 100,000 ng/ml |
| (-)-11-Nor-Δ9-THC | 500,000 ng/ml |
| Carboxylic Acid | |
| Niflumic Acid | 100,000 ng/ml |
| Amlodipine besylate | 100,000 ng/ml |
| Doxylamine succinate salt | 100,000 ng/ml |
| Amoxicillin Trihydrate | 500,000 ng/ml |
| Atorvastatin Calcium Salt | 100,000 ng/ml |
| Hydroxyzine Pamoate | 100,000 ng/ml |
| Compound Losartan | 100,000 ng/ml |
| Chlorpheniramine | 100,000 ng/ml |
| Prochlorperazine | 25,000 ng/ml |
| D-(+)-Amphetamine Sulfate | 500,000 ng/ml |
| Pentobarbital | 500,000 ng/ml |
| Buprenorphine hydrochloride | 100,000 ng/ml |
| (+)-Lorazepam | 500,000 ng/ml |
| Oxycodone Hydrochloride | 100,000 ng/ml |
| Fluphenazine | 100,000 ng/ml |
| Methapyrilene | 50,000 ng/ml |
| Calcium Chloride | 3 mg/ml |
| Sodium Phosphate Dibasic | 3 mg/ml |
| DL β-Hydroxybutyric Acid | 1 mg/ml |
| Uric Acid | 100,000 ng/ml |
| Fentanyl | 100,000 ng/ml |
| Pethidine HCL (Meperidine HCl) | 500,000 ng/ml |
| Dextropropoxyphene | 500,000 ng/ml |
| Zolpidem-6-Carboxylic Acid | 10,000 ng/ml |
| Oxymorphone | 100,000 ng/ml |
| (±)-MDMA | 100,000 ng/ml |
| 6-Acetylmorphine | 100,000 ng/ml |
| (±)-MDA | 100,000 ng/ml |
| Amitriptyline HCl | 125,000 ng/ml |
| Verapamil HCL | 500,000 ng/ml |
| Zolpidem Phenyl-4- | 10,000 ng/ml |
| Carboxylic Acid | |
| Thioridazine | 250,000 ng/ml |
| JWH-073 | 500,000 ng/ml |

{10}

K221550 - Page 11 of 18

| Interference: Phencyclidine Assay | |
| --- | --- |
| Compound | Concentration Tested |
| Acetone | 1000 mg/dl |
| Ethanol | 1000 mg/dl |
| Glucose | 3000 mg/dl |
| Oxalic Acid | 100 mg/dl |
| Sodium Chloride | 6000 mg/dl |
| Caffeine | 1 mg/ml |
| Ascorbic Acid | 1500 mg/dl |
| Galactose | 10 mg/dl |
| Hemoglobin | 300 mg/dl |
| Riboflavin | 7.5 mg/dl |
| Acetaminophen | 1 mg/ml |
| Ibuprofen | 1 mg/ml |
| Creatinine | 5 mg/ml |
| Gamma Globulin | 500 mg/dl |
| Human Serum Albumin | 500 mg/dl |
| Urea | 3500 mg/dl |
| Acetylsalicylic Acid | 1 mg/ml |
| Ranitidine | 0.9 mg/ml |
| Imipramine HCL | 25,000 ng/ml |
| Benzocaine | 100,000 ng/ml |
| Erythromycin | 100,000 ng/ml |
| Furosemide | 100,000 ng/ml |
| Diphenhydramine HCl | 5,000 ng/ml (Positive Interference) |
| Penicillin G | 100,000 ng/ml |
| Atropine Sulfate | 25,000 ng/ml |
| Quinidine | 100,000 ng/ml |
| (-)-isoproterenol HCl | 100,000 ng/ml |
| Lidocaine | 500,000 ng/ml |
| Dextromethorphan hydrobromide monohydrate | 25,000 ng/ml |
| Aspartame | 100,000 ng/ml |
| Guaiacol Glyceryl Ether | 100,000 ng/ml |
| Sulindac | 100,000 ng/ml |
| Chlorpheniramine | 100,000 ng/ml |
| Pheniramine | 10,000 ng/ml |
| Amitriptyline HCl | 50,000 ng/ml |
| Interference: Buprenorphine Assay | |
| --- | --- |
| Compound | Concentration Tested |
| Acetone | 1000 mg/dl |
| Ethanol | 1000 mg/dl |

{11}

K221550 - Page 12 of 18

| Glucose | 3000 mg/dl |
| --- | --- |
| Oxalic Acid | 100 mg/dl |
| Sodium Chloride | 6000 mg/dl |
| Caffeine | 1 mg/ml |
| Ascorbic Acid | 1500 mg/dl |
| Galactose | 10 mg/dl |
| Hemoglobin | 300 mg/dl |
| Riboflavin | 7.5 mg/dl |
| Acetaminophen | 1 mg/ml |
| Ibuprofen | 1 mg/ml |
| Creatinine | 5 mg/ml |
| Gamma Globulin | 500 mg/dl |
| Human Serum Albumin | 500 mg/dl |
| Urea | 3500 mg/dl |
| Acetylsalicylic Acid | 1 mg/ml |
| Ranitidine | 0.9 mg/ml |
| Interference: 6-Acetylmorphine Assay | |
| --- | --- |
| Compound | Concentration Tested |
| Acetone | 1000 mg/dl |
| Ethanol | 1000 mg/dl |
| Glucose | 3000 mg/dl |
| Oxalic Acid | 100 mg/dl |
| Sodium Chloride | 6000 mg/dl |
| Caffeine | 1 mg/ml |
| Ascorbic Acid | 1500 mg/dl |
| Galactose | 10 mg/dl |
| Hemoglobin | 300 mg/dl |
| Riboflavin | 7.5 mg/dl |
| Acetaminophen | 1 mg/ml |
| Ibuprofen | 1 mg/ml |
| Creatinine | 5 mg/ml |
| Gamma Globulin | 500 mg/dl |
| Human Serum Albumin | 500 mg/dl |
| Urea | 3500 mg/dl |
| Acetylsalicylic Acid | 1 mg/ml |
| Ranitidine | 0.1 mg/ml |
| Salbutamol | 100,000 ng/ml |
| Digoxin | 500,000 ng/ml |
| Fluoxetine HCl | 500,000 ng/ml |
| Diphenhydramine HCl | 500,000 ng/ml |
| Oxazepam | 500,000 ng/ml |
| Phenobarbital | 500,000 ng/ml |
| (±)-Methadone Hydrochloride | 500,000 ng/ml |
| (+) - Methamphetamine Hydrochloride | 500,000 ng/ml |
| Chlorpromazine HCl | 500,000 ng/ml |

{12}

K221550 - Page 13 of 18

| Desipramine Hydrochloride | 500,000 ng/ml |
| --- | --- |
| Doxepin Hydrochloride | 200,000 ng/ml |
| Benzoylecgonine Tetrahydrate | 500,000 ng/ml |
| (-)-11-Nor-Δ9-THC Carboxylic Acid | 500,000 ng/ml |
| Triprolidine Hydrochloride | 100,000 ng/ml |
| Hydroxyzine | 500,000 ng/ml |
| Brompheniramine Maleate | 250,000 ng/ml |
| Diazepam | 500,000 ng/ml |
| Dextropropoxyphene | 500,000 ng/ml |
| Phencyclidine | 100,000 ng/ml |
| Amitriptyline HCl | 500,000 ng/ml |
| Secobarbital | 100,000 ng/ml |

## Analytical Specificity:

To test cross-reactivity, drug metabolites and other compounds that may be present in human urine samples were tested using three (3) lots of the candidate device. The sponsor identified the concentration of each compound prepared in drug free negative urine that would produce a positive response for each assay when analyzed against the cut off material. The following is a summary of the cross-reactivity study. The individual assays are calibrated against the compounds marked with an asterisk (*).

| Phenobarbital Assay Specificity | Concentration which resulted in positive (ng/ml) | Percent (%) Cross Reactivity |
| --- | --- | --- |
| Phenobarbital* | 200 | 100.0 |
| Secobarbital | 50 | 400.0 |
| Butabarbital | 70 | 285.7 |
| Alphenal | 90 | 222.2 |
| Pentobarbital | 90 | 222.2 |
| Cyclopentobarbital | 200 | 100.0 |
| Amobarbital | 210 | 95.2 |
| Butalbital | 210 | 95.2 |
| Barbital | 250 | 80.0 |
| 4-Hydroxypentobarbital | 225 | 88.9 |
| Tramadol Assay Specificity | Concentration which resulted in positive (ng/ml) | Percent (%) Cross Reactivity |
| --- | --- | --- |
| Tramadol* | 200 | 100.0 |
| N-Desmethyl-cis-tramadol | 1,100 | 18.2 |
| O-Desmethyl-cis-tramadol | 3,000 | 6.7 |
| O-Desmethyl Tramadol β-D-Glucuronide | 200,000 | 0.1 |
| rac N-O-Didesmethyl tramadol | 15,000 | 1.3 |

{13}

K221550 - Page 14 of 18

| Ketamine | Neg @ 100,000ng/ml | Not Detected |
| --- | --- | --- |
| (±)-Norketamine | Neg @ 20,000ng/ml | Not Detected |
| Dehydro-Norketamine | Neg @ 10,000ng/ml | Not Detected |
| O-Desmethylvenlafaxine | Neg @ 200,000ng/ml | Not Detected |
| Venlafaxine | Neg @ 100,000ng/ml | Not Detected |
| Naproxen | Neg @ 100,000ng/ml | Not Detected |
| Phencyclidine Assay Specificity | Concentration which resulted in positive (ng/ml) | Percent (%) Cross Reactivity |
| --- | --- | --- |
| Phencyclidine* | 25 | 100.0 |
| Tenocyclidine (TCP) | 125 | 20.0 |
| Fentanyl | 45,000 | 0.1 |
| Diphenhydramine¹ | 100,000 ng/ml | 0.025 |
| Dextromethorphan Hydrobromide Monohydrate | 1,000,000 ng/ml | 0.003 |
| Venlafaxine | Neg @ 100,000 ng/ml | Not Detected |

¹ Diphenhydramine also demonstrated positive interference at 5,000 ng/ml.

| Buprenorphine Assay Specificity | Concentration which resulted in positive (ng/ml) | Percent (%) Cross Reactivity |
| --- | --- | --- |
| Norbuprenorphine* | 5 | 100.0 |
| Buprenorphine | 30 | 16.7 |
| Norbuprenorphine Glucuronide | 35 | 14.3 |
| Buprenorphine-3 β-D-glucuronide | 210 | 2.4 |
| EMDP | Neg @ 100,000 ng/ml | Not Detected |
| Heroin | Neg @ 100,000 ng/ml | Not Detected |
| Levorphanol Tartrate | Neg @ 150,000 ng/ml | Not Detected |
| 6-Acetylmorphine Assay Specificity | Concentration which resulted in positive (ng/ml) | Percent (%) Cross Reactivity |
| --- | --- | --- |
| 6-Acetylmorphine* | 10 | 100.0 |
| Heroin | 1,200 | 0.8 |
| 6-Acetylcodeine | 1,500 | 0.7 |
| Levorphanol Tartrate | 150,000 | 0.007 |
| Codeine | Neg @ 100,000 ng/ml | Not Detected |
| Codeine-6-β-D-Glucuronide | Neg @ 100,000 ng/ml | Not Detected |
| Desomorphine | Neg @ 10,000 ng/ml | Not Detected |
| Dextromethorphan Hydrobromide Monohydrate | Neg @ 1,000,000 ng/ml | Not Detected |
| Dihydrocodeine | Neg @ 100,000 ng/ml | Not Detected |
| Ethyl Morphine | Neg @ 10,000 ng/ml | Not Detected |
| Hydrocodone | Neg @ 100,000 ng/ml | Not Detected |

{14}

K221550 - Page 15 of 18

| Hydromorphone | Neg @ 100,000 ng/ml | Not Detected |
| --- | --- | --- |
| Imipramine HCL | Neg @ 200,000 ng/ml | Not Detected |
| Morphine | Neg @ 100,000 ng/ml | Not Detected |
| Morphine-3 βD-glucuronide | Neg @ 10,000 ng/ml | Not Detected |
| Morphine-6 βD-glucuronide | Neg @ 600,000 ng/ml | Not Detected |
| Naloxone | Neg @ 500,000 ng/ml | Not Detected |
| Nalorphine | Neg @ 200,000 ng/ml | Not Detected |
| Naltrexone | Neg @ 300,000 ng/ml | Not Detected |
| Norcodeine | Neg @ 100,000 ng/ml | Not Detected |
| Norhydrocodone | Neg @ 100,000 ng/ml | Not Detected |
| Normorphine | Neg @ 100,000 ng/ml | Not Detected |
| Noroxycodone | Neg @ 50,000 ng/ml | Not Detected |
| Noroxymorphone HCL | Neg @ 200,000 ng/ml | Not Detected |
| Oxycodone | Neg @ 100,000 ng/ml | Not Detected |
| Oxymorphone | Neg @ 100,000 ng/ml | Not Detected |
| Oxymorphone-3-β-D-Glucuronide | Neg @ 30,000 ng/ml | Not Detected |
| Pethidine HCl (Meperidine HCl) | Neg @ 200,000 ng/ml | Not Detected |
| Thebaine | Neg @ 10,000 ng/ml | Not Detected |

## Specificity of Structurally Related Compounds:

The following structurally unrelated compounds were tested and were found not to be detected when measuring any of the claimed drugs (Phenobarbital, Tramadol, Phencyclidine, Buprenorphine, 6-Acetylmorphine).

### Specificity of Structurally Unrelated Compounds:

| Compound | Approximate Concentration to Read Positive | Approximate Percent (%) Cross Reactivity |
| --- | --- | --- |
| S(+)-Methamphetamine | Neg @ 50,000 ng/ml | Not Detected |
| S(+)-Amphetamine | Neg @ 50,000 ng/ml | Not Detected |
| Phenobarbital | Neg @ 50,000 ng/ml | Not Detected |
| Oxazepam | Neg @ 50,000 ng/ml | Not Detected |
| Lorazepam | Neg @ 50,000 ng/ml | Not Detected |
| (-)-11-nor-9-Carboxy- Δ9-THC | Neg @ 50,000 ng/ml | Not Detected |
| Benzoylecgonine | Neg @ 50,000 ng/ml | Not Detected |
| (+)-Methadone | Neg @ 50,000 ng/ml | Not Detected |
| Morphine | Neg @ 50,000 ng/ml | Not Detected |
| Fentanyl | Neg @ 50,000 ng/ml | Not Detected |
| Noroxycodone | Neg @ 50,000 ng/ml | Not Detected |
| Tramadol | Neg @ 50,000 ng/ml | Not Detected |
| 6-Acetylmorphine | Neg @ 50,000 ng/ml | Not Detected |
| PCP | Neg @ 50,000 ng/ml | Not Detected |

{15}

K221550 - Page 16 of 18

# Specific gravity and pH:

The effect of specific gravity for each analyte was evaluated by testing positive (50% above cutoff) and negative samples (50% below cutoff) at specific gravities ranging from 1.000 to 1.030. No interference was observed for all specific gravities tested.

The sponsor performed a study to evaluate whether low or high pH causes negative or positive interference with the candidate device. Samples containing the claimed drugs at concentrations corresponding to -50% and +50% of the cutoff were adjusted to pH levels ranging from 3.0 to 11.0. Aside from 6-Acetylmorphine at pH 11, none of the pH levels tested caused a positive result at -50% of the cutoff or a negative result at +50% of the cutoff, as described below:

| Assay | pH Assessed that Does Not Interfere | | | | |
| --- | --- | --- | --- | --- | --- |
| | pH 3 | pH 5 | pH 7 | pH 9 | pH 11 |
| Phenobarbital | No effect | No effect | No effect | No effect | No effect |
| Tramadol | No effect | No effect | No effect | No effect | No effect |
| Phencyclidine | No effect | No effect | No effect | No effect | No effect |
| Buprenorphine | No effect | No effect | No effect | No effect | No effect |
| 6-Acetylmorphine | No effect | No effect | No effect | No effect | Interference Observed |
| Effect of pH: 6-Acetylmorphine | | | | | |
| Compound | Value | -50% Cut Off (5.0ng/mL) | | +50% Cut Off (15.0ng/mL) | |
| | | Result | Interference? | Result | Interference? |
| pH | 10 | Negative | No | Positive | No |
| | 11 | Negative | No | Negative | Yes |

4. Assay Reportable Range:
Not applicable.

5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):
The assays are traceable to commercially available standards.

6. Detection Limit:
Not applicable.

7. Assay Cut-Off:
Not applicable.

B Comparison Studies:

1. Method Comparison with Predicate Device:

{16}

A method comparison study was conducted using 878 clinical samples obtained from one (1) site and tested on the candidate device and compared to results from a LC-MS/MS quantitative comparator method. Phenobarbital results were compared to results from a GC/MS quantitative comparator method. Results are summarized below.

| Analyte | N | Cut-Off (ng/ml) | Evidence MultSTAT Urine MultiPlex Result | Reference Method Results by GC/MS or LC-MS/MS Value | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | Low Negative Less than 50% below the Cut Off | Near Cut Off Negative Between 50% below the Cut Off | Near Cut Off Positive Between 50% above the Cut Off | High Positive Greater than 50% above the Cut Off |
| Phenobarbital | 111 | 200 | Positive | 0 | 7 | 21 | 40 |
| | | | Negative | 41 | 2 | 0 | 0 |
| Tramadol | 287 | 200 | Positive | 0 | 3 | 6 | 41 |
| | | | Negative | 235 | 2 | 0 | 0 |
| Phencyclidine (PCP) | 132 | 25 | Positive | 2* | 6 | 11 | 46 |
| | | | Negative | 64 | 3 | 0 | 0 |
| Buprenorphine | 108 | 5 | Positive | 0 | 0 | 4 | 40 |
| | | | Negative | 49 | 12 | 3 | 0 |
| 6-Acetylmorphine (6-MAM) | 240 | 10 | Positive | 0 | 3 | 5 | 45 |
| | | | Negative | 185 | 2 | 0 | 0 |

**Discordant Sample Results:**

* - These samples contained diphenhydramine at levels shown to cause positive interference.

2. **Matrix Comparison:**

Not applicable.

**C Clinical Studies:**

1. **Clinical Sensitivity:**

Not applicable.

2. **Clinical Specificity:**

Not applicable.

3. **Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):**

K221550 - Page 17 of 18

{17}

Not applicable.

## D Clinical Cut-Off:
Not applicable.

## E Expected Values/Reference Range:
Not applicable.

## VIII Proposed Labeling:
The labeling supports the finding of substantial equivalence for this device.

## IX Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

K221550 - Page 18 of 18